Figure 4. Promising therapeutic algorithm in the near future.

Nivolumab and cabozantinib are superior to everolimus in patients who have failed one line or more of VEGF targeted therapy (CheckMate 025 study; METEOR study). Nivolumab showed delayed benefit in PFS versus everolimus. The progression-free survival curves has a late separation in the study. Therefore it would seem reasonable to use it in fit patients with slow progression. Cabozantinib is a multi-tyrosine kinase inhibitor. For its impressive PFS versus everolimus (cabozantinib median PFS 7.4 mo; everolimus median PFS 3.8 mo) should be considered for patients with rapid progression. No trials have compared these two experimental agents directly against axitinib in the second-line setting, where axitinib showed no OS advantage. Survival advantage and tolerability profile of nivolumab over everolimus makes it a valid option also versus axitinib.